Fluoroquinolone antimicrobial agents are highly active against aerobic or facultative gram-negative bacilli. The fluoroquinolones have been shown to be very concentration dependent in their rates of killing and also have a postantibiotic effect against most gram-negative pathogens. These properties resemble those of aminoglycosides more than those of the beta-lactam antibiotics. In animal studies, once daily administration of a dose that produced a high peak concentration/minimal inhibitory concentration (MIC) ratio of > 10-20:1 resulted in significantly better survival than did regimens in which the same daily dose was used on a more fractionated schedule. Studies in patients, most often with ciprofloxacin, demonstrated that the area under the concentration-time curve (AUC)/MIC ratio (AUIC) is the most important predictor of both clinical and microbiological cure. These findings, when combined with microbiological and pharmacokinetic data, provide the rationale and tools needed for targeting the dosage of fluoroquinolones to individual patients on the basis of pharmacokinetics and the susceptibilities of the bacterial pathogens.

In an open, randomized, six-period crossover study, the pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin were compared after a single oral dose in 12 healthy volunteers (6 men and 6 women). The volunteers received 250 mg of ciprofloxacin, 400 mg of gatifloxacin, 600 mg of grepafloxacin, 500 mg of levofloxacin, 400 mg of moxifloxacin, and 200 mg of trovafloxacin. The concentrations of the six fluoroquinolones in serum and urine were measured by a validated high-performance liquid chromatography method. Blood and urine samples were collected before and at different time points up to 48 h after medication. Levofloxacin had the highest peak concentration (C max , in micrograms per milliliter) (6.21 ؎ 1.34), followed by moxifloxacin (4.34 ؎ 1.61) and gatifloxacin (3.42 ؎ 0.74). Elimination half-lives ranged from 12.12 ؎ 3.93 h (grepafloxacin) to 5.37 ؎ 0.82 h (ciprofloxacin). The total areas under the curve (AUC tot , in microgram-hours per milliliter) for levofloxacin (44.8 ؎ 4.4), moxifloxacin (39.3 ؎ 5.35), and gatifloxacin (30 ؎ 3.8) were significantly higher than that for ciprofloxacin (5.75 ؎ 1.25). Calculated from a normalized dose of 200 mg, the highest C max s (in micrograms per milliliter) were observed for levofloxacin (2.48 ؎ 0.53), followed by moxifloxacin (2.17 ؎ 0.81) and trovafloxacin (2.09 ؎ 0.58). The highest AUC tot (in microgram-hours per milliliter) for a 200-mg dose were observed for moxifloxacin (19.7 ؎ 2.67) and trovafloxacin (19.5 ؎ 3.1); the lowest was observed for ciprofloxacin (4.6 ؎ 1.0). No serious adverse event was observed during the study period. The five recently developed fluoroquinolones (gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin) showed greater bioavailability, longer half-lives, and higher C max s than ciprofloxacin.Fluoroquinolones are widely used alternatives to ␤-lactam agents in the treatment of many bacterial infections. Their antimicrobial activity results from a selective antagonism between host DNA and bacterial DNA without interfering with eucaryotic topoisomerases. The early fluoroquinolones, from the early 1960s, had a limited spectrum of antibacterial activity, mainly against gram-negative pathogens. Further observations of structure-related increases in activity, changes in pharmacokinetic characteristics, and reduced toxicity were followed by numerous chemical modifications of the quinolone molecule. The resulting new fluoroquinolone antimicrobial agents have enhanced activity against gram-positive organisms and anaerobes (1, 2) and improved pharmacokinetic parameters in comparison to previous derivatives. However, only reports on single-drug kinetics have been published so far, and there have been no direct comparisons between the new drugs and the standard drug, ciprofloxacin (1-3).We therefore evaluated and compared the pharmacokinetics of six fluoroquinolones after a single oral dose in the same volunteers.( (mean, 28.4 Ϯ 4.3 years) and with an average weight of 67.4 ...

In 12 fasting volunteers, the pharmacokinetics of ciprofloxacin (Bay o 9867; 1-cyclopropyl-6-fluor-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carbonic acid) were determined after the administration of 50, 100, and 750 mg orally as well as 50 and 100 mg intravenously over 15 min. Serum

In 10 volunteers, the pharmacokinetics of ofloxacin {HOE 280, DL 8280; (+)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido-[1,2,3-deI [1,4] 1.4 liters/kg of body weight) suggested effective diffusion into the extravascular space. High total and renal clearances indicated primarily renal excretion with additional elimination pathways, such as tubular secretion and extrarenal elimination. After oral administration, absorption was excellent, and the absolute bioavailability following 200 mg of ofloxacin could be calculated at >0.95. Maximal concentrations in serum were attained 1.2 to 1.9 h after dosing; areas under the curve increased in proportion to dose between 200 and 400 mg of oral ofloxacin. The amount of known metabolites (demethyl and N-oxide compounds) excreted in urine reached only 4.3% (intravenously) and 4.0% (orally). Transient headaches in some volunteers were the only side effects registered.6-Fluoro-7-piperazino-4-quinolones are noteworthy both for the wide range and intensity of activities against gramnegative bacilli and cocci in vitro and the capacity to control experimentally induced systemic infections with selected bacteria when administered orally in well-tolerated doses (9,15,27).Ofloxacin {HOE 280, DL 8280; (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl) -7-oxo-7H-pyrido[1,2,3-de] [1,4]benzoxacine-6-carboxylic acid} is a new quinolone carboxylic acid derivative showing a broad antimicrobial spectrum against gram-positive and gram-negative bacteria (1,11,17,22,27). This substance was found to be more active than norfloxacin and pipemidic acid (22), its in vitro antibacterial activity being almost comparable to those of gentamicin, tobramycin, and newer cephalosporins (9,11,27). When first introduced, ofloxacin could only be administered orally, but recently a parenteral form was developed.The purpose of this study was to investigate the pharmacokinetic properties of this quinolone after oral and intravenous (i.v.) administration of various doses to determine the bioavailability and metabolism of this drug.(Part of this study was presented at the 24th Interscience

One of the chemical features that distinguishes the 15-membered ring azalide azithromycin from the 14-membered ring macrolide compound erythromycin is the former's increased stability at acid pH. Azithromycin also differs pharmacokinetically from erythromycin, an important feature being azithromycin's ability to achieve high tissue concentrations, with the agent being delivered to the sites of infection by direct uptake and by targeted delivery via phagocytes. High tissue concentrations are maintained for prolonged periods because of azithromycin's long half-life, leading to once-daily dosing for 3 or 5 days. Notable microbiological features of azithromycin are in-vitro activity against many pyogenic bacteria (e.g. Neisseria gonorrhoeae and Moraxella catarrhalis), as well as organisms against which beta-lactam antibiotics are usually ineffective (e.g. Legionella and Chlamydia spp.), organisms that are resistant to benzylpenicillin and erythromycin (e.g. Haemophilus influenzae) and organisms for which satisfactory therapy is limited (e.g. Toxoplasma gondii and the Mycobacterium avium-intracellulare complex). These properties of azithromycin suggest that it might be a useful agent for the treatment of a wide range of bacterial infections.